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A novel multiplex-protein array for serum diagnostics of colon cancer: a case–control study

机译:用于结肠癌血清诊断的新型多重蛋白阵列:病例对照研究

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Background More than 1.2 million new cases of colorectal cancer are reported each year worldwide. Despite actual screening programs, about 50% of the patients are diagnosed at advanced tumor stages presenting poor prognosis. Innovative screening tools could aid the detection at early stages and allow curative treatment interventions. Methods A nine target multiplex serum protein biochip was generated and evaluated using a training- and validation-set of 317 highly standardized, liquid nitrogen preserved serum samples comprising controls, adenomas, and colon cancers. Results Serum levels of CEA, IL-8, VEGF, S100A11, MCSF, C3adesArg, CD26, and CRP showed significant differences between cases and controls. The largest areas under the receiver operating characteristics curve were observed for CEA, IL-8, and CRP. At threshold levels yielding 90% specificity, sensitivities for CEA, IL-8 and CRP were 26%, 22%, and 17%, respectively. The most promising marker combinations were CEA?+?IL-8 reaching 37% sensitivity at 83% specificity and CEA?+?CRP with 35% sensitivity at 81% specificity. In an independent validation set CEA?+?IL-8 reached 47% sensitivity at 86% specificity while CEA?+?CRP obtained 39% sensitivity at 86% specificity. Early carcinomas were detected with 33% sensitivity for CEA?+?IL-8 and 28% for CEA?+?CRP. Conclusions Apart from CEA, IL-8, and CRP, the screening value of additional blood markers and the potential advantage of combining serum biochip testing with fecal occult blood testing needs to be studied. Multiplex biochip array technology utilizing serum samples offers an innovative approach to colorectal cancer screening.
机译:背景技术全世界每年报告超过120万例大肠癌新病例。尽管有实际的筛查程序,约50%的患者被诊断为晚期肿瘤,预后较差。创新的筛查工具可以帮助早期发现并允许治疗性干预。方法使用317个高度标准化,液氮保存的血清样本(包括对照,腺瘤和结肠癌)的训练集和验证集,生成并评估了9个目标多重血清蛋白生物芯片。结果血清CEA,IL-8,VEGF,S100A11,MCSF,C3adesArg,CD26和CRP的水平在病例与对照组之间存在显着差异。对于CEA,IL-8和CRP,观察到接收器工作特性曲线下的最大面积。在产生90%特异性的阈值水平下,对CEA,IL-8和CRP的敏感性分别为26%,22%和17%。最有前途的标志物组合是:CEAα+βIL-8在83%的特异性下达到37%的敏感性和CEAβ+βCRP在81%的特异性下达到35%的敏感性。在一个独立的验证集中,CEAα+βIL-8在86%的特异性下达到了47%的敏感性,而CEAβ+βCRP在86%的特异性下获得了39%的敏感性。检出的早期癌对CEAβ+ IL-8的敏感性为33%,对CEAβ+ CRP的敏感性为28%。结论除了CEA,IL-8和CRP外,还需要研究其他血液标志物的筛查价值以及将血清生物芯片检测与粪便潜血检测相结合的潜在优势。利用血清样品的多重生物芯片阵列技术为结肠直肠癌筛查提供了一种创新方法。

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